The Role of the Cerebellum in Schizophrenia: an Update of Clinical, Cognitive, and Functional Evidences

Abstract

The role of the cerebellum in schizophrenia has been highlighted by Andreasen's hypothesis of “cognitive dysmetria,” which suggests a general dyscoordination of sensorimotor and mental processes. Studies in schizophrenic patients have brought observations supporting a cerebellar impairment: high prevalence of neurological soft signs, dyscoordination, abnormal posture and propioception, impaired eyeblink conditioning, impaired adaptation of the vestibular-ocular reflex or procedural learning tests, and lastly functional neuroimaging studies correlating poor cognitive performances with abnormal cerebellar activations. Despite those compelling evidences, there has been, to our knowledge, no recent review on the clinical, cognitive, and functional literature supporting the role of the cerebellum in schizophrenia. We conducted a Medline research focusing on cerebellar dysfunctions in schizophrenia. Emphasis was given to recent literature (after 1998). The picture arising from this review is heterogeneous. While in some domains, the role of the cerebellum seems clearly defined (ie, neurological soft signs, posture, or equilibrium), in other domains, the cerebellar contribution to schizophrenia seems limited or indirect (ie, cognition) if present at all (ie, affectivity). Functional models of the cerebellum are proposed as a background for interpreting these results.

Lower number of cerebellar Purkinje neurons in psychosis is associated with reduced reelin expression

“…We can infer that the down-regulation of GAD67 in Purkinje cells contributes to the dysfunction of cerebellar-dentate-prefrontal cortex circuitry (32,33) in SZ, which could also be one reason for the psychiatric symptoms and neurologic abnormalities, such as the altered coordination of limbic movements (1,26,33), found in these patients.…”

The Role of the Cerebellum in Schizophrenia

“…His work was followed by multiple additional studies using anatomical imaging tools such as CT and later morphometric Magnetic Resonance (mMR) that have reported abnormalities in cerebellar size in schizophrenia (50-57). Picard et al (58) recently conducted a review of the evidence for cerebellar abnormalities in schizophrenia from multiple perspectives: symptoms, neurological signs, eye movements, nondeclarative learning, and cognition. They conclude that evidence for cerebellar abnormalities is strong from some perspectives (e.g., neurological soft signs, posture, equilibrium) but that the evidence for other domains such as cognition is more heterogeneous.…”

High‐angular resolution diffusion imaging tractography of cerebellar pathways from newborns to young adults

“…Lesions in the cerebellum have resulted in disorders of executive function (Courchesne et al., 1994; Tanaka, Harada, Arai, & Hirata, 2003), visuospatial abilities (Fabbro et al., 2004; Schmahmann & Sherman, 1998), expressive language (Fabbro et al., 2004; Molinari, Leggio, & Silveri, 1997), and affective behavior (Courchesne et al., 1994; Schmahmann, 2000), among others. Cerebellar dysfunction has also been implicated in disorders such as such autism (Courchesne et al., 1994; Fatemi et al., 2012; Penn, 2006), schizophrenia (Lungu et al., 2013; Picard, Amado, Mouchet‐Mages, Olié, & Krebs, 2008; Varambally, Venkatasubramanian, Thirthalli, Janakiramaiah, & Gangadhar, 2006), depression (Beyer & Krishnan, 2002; Leroi et al., 2002), and bipolar disorder (Beyer & Krishnan, 2002; Mills, Delbello, Adler, & Strakowski, 2005). Some of these disorders have been shown to specifically involve the cerebellar peduncle pathways (Hanaei et al., 2013; Hüttlova et al., 2014; Ojemann et al., 2013; Wang, Fan, Xu, & Wang, 2014; Wang et al., 2003, 2003, 2014) and an understanding of the development of these pathways may aid in elucidating our understanding of the development and etiology of these disorders as well as to create related diagnostic technologies.…”